The Oxford study of calcium channel antagonism, cognition, mood instability and sleep

INTERVENTION: The intervention is nicardipine or placebo. The design is as follows. There is a 14‐day run‐in phase (when participants undergo functional brain imaging and complete repeated assessments of mood, cognition, activity and sleep). On day 15, participants are randomised, double‐blind, to nicardipine (Cardene) sustained release (SR), 30 mg oral capsule twice a day, or matched placebo, for another 14 days. During this period, all assessments and scans are repeated, with participants and investigators remaining blind to treatment allocation. CONDITION: Mood instability, which is a feature of bipolar disorder and other psychiatric disorders including borderline personality disorder, but can also occur in the absence of any diagnosis ; Mental and Behavioural Disorders PRIMARY OUTCOME: 1. Cognitive variability, measured at varying time points and evaluated using a range of cognitive tasks, comprising: ; 1.1. The N‐Back task of working memory (baseline and study endpoint); 1.2. The Stop‐Signal task (baseline and study endpoint); 1.3. The theory of visual attention (TVA) (baseline and study endpoint); 1.4. The emotional test battery (ETB) (baseline and study endpoint); 1.5. ‘Wheel of fortune’ (daily over the 4‐week study period); 1.6. Whack‐A‐T (daily over the 4‐week study period); 1.7. Fractals (daily over the 4‐week study period) SECONDARY OUTCOME: 1. Blood oxygen level dependent signal during rest and during cognitive testing (fMRI); induced and evoked field activity (MEG); measured pre‐ and post‐ randomisation to nicardipine/placebo, on study days 14 and 28 respectively; 2. Activity monitored by Geneactiv watch (daily over the 4‐week study period); 2.1. Actigraphy data from a maximum of two wearable units, allowing analysis of indices of:; 2.1.1. Frequency and amplitude of movements during daytime activity; 2.1.2. Categorisation of activity types; 2.1.3. Duration, timing, and quality of sleep; 2.2. Sleep quality indicator questionnaire, measured at baseline and post‐randomisation to nicardipine/placebo; 3. Leucocyte calcium channel expression and calcium signalling, measured using qPCR quantification of calcium channel subunit transcripts and Fura dye imaging of calcium fluxes, at baseline and study endpoint; 4. Heart rate (R‐R interval) variability, measured by ePatch fitted at baseline visit for 72 hours, and again three days after commencing nicardipine/placebo for a further 72 hours; 5. Mood instability as defined using root mean square of the successive differences (RMSSD), measured by twice daily PANAS questionnaire over the 4‐week study period INCLUSION CRITERIA: Healthy volunteers with score of =7 on the Mood Disorder Questionnaire (MDQ) with evidence of associated functional impairment: 1. Willing and able to given informed consent to participate in the study 2. Male or female 3. Aged 18 – 35 4. Significant mood instability (defined as a score of =7 on the Mood Disorder Questionnaire) causing at least mild dysfunction 5. No indication that urgent psychiatric treatment is required 6. Pre‐treatment tests including renal, cardiac and liver function acceptable for the initiation of treatment with nicardipine 7. Willing and able to comply with the study requirements 8. Willing to allow his/her General Practitioner, if appropriate, to be notified of his/her participation in the study